Circular Dichroism Studies of the Structure of DNA Complex with Berberine

Abstract

The binding of the benzodioxolo-benzoquinolizine alkaloid, berberine chloride to natural and synthetic DNAs has been studied by intrinsic and extrinsic circular dichroic measurements. Binding of berberine causes changes in the circular dichroism spectrum of DNA as shown by the increase of molar ellipticity of the 270nm band, but with very little change of the 240nm band. The molar ellipticity at the saturation depends strongly on the base composition of DNA and also on salt concentration, but always larger for the AT rich DNA than the GC rich DNA. The features in the circular dichroic spectral changes of berberine-synthetic DNA complexes were similar to that of native DNA, but depends on the sequence of base pairs. On binding to DNA and polynucleotides, the alkaloid becomes optically active. The extrinsic circular dichroism developed in the visible absorption region (300-500nm) for the berberine-DNA complexes shows two broad spectral bands in the regions 425-440nm and 340-360nm with the maximum varying depending on base composition and sequence of DNA. While the 425nm band shows less variation on the binding ratio, the 360nm band is remarkably dependent on the DNA/alkaloid ratio. The generation of the alkaloid associated extrinsic circular dichroic bands is not dependent on the base composition or sequence of base pairs, but the nature and magnitude of the bands are very much dependent on these two factors and also on the salt concentration. The interpretation of the results with respect to the modes of the alkaloid binding to DNA are presented.

Capillary zone electrophoretic studies of interactions of some quaternary isoquinoline alkaloids with DNA constituents and DNA

“…Coulombic attraction participates in the interaction according to our measurements but other kinds of intermolecular forces play a significant role as well. No significant difference was observed between the behavior of alkaloids and ET, therefore, the intercalative interaction mode being already reported for SA, CHE, and BE [7][8][9] was confirmed for these alkaloids. Our results also suggest that JA, which, to our knowledge, was not yet studied for interaction with DNA, intercalates to DNA as well.…”

“…The results of our experiments together with informations in the literature [7][8][9] about the mode of interaction of the alkaloids with DNA clearly show that intact alkaloids interact with DNA solely noncovalently by forming a kinetically labile complex. The contradictory arguments reported in the literature suggesting other modes of interaction [10][11][12][13][14] are probably a consequence of metabolic activation of the alkaloids inside the living organisms.…”

“…For example, the interaction of various QIAs with DNA has been repeatedly investigated and intercalation was concluded as the mode of interaction in most of the studies [7][8][9]. However, this mechanism cannot entirely explain all known facts about the alkaloids' action in biological systems, such as the mutagenic action being reported for sanguinarine (SA) [10] and chelerythrine (CHE) [11] as the most important quaternary benzo[c]-phenanthridine alkaloids as well as for berberine (BE) [12], the most important quaternary protoberberine alkaloid.…”

Evaluation of the antimicrobial mode of berberine by LC/ESI-MS combined with principal component analysis

“…According to the principle of PCA, the mode of berberine should be similar with that of Rifampicin and Norfloxacin. That is, its target is possibly on nucleic acid, which also has been documented by other methods [10][11][12][13][14][15][16].…”

Molecular aspects on the interaction of protoberberine, benzophenanthridine, and aristolochia group of alkaloids with nucleic acid structures and biological perspectives

“…The authors laboratory [125][126][127][128][129] have first demonstrated the base and sequence specificity of berberine from studies with several naturally occurring and synthetic DNAs of differing base composition and sequences. The binding of berberine to B-DNA was characterized by hypochromism and bathochromism in the absorption spectrum (Fig.…”